Analysis of marginal zone B cell development in the mouse with limited B cell diversity: Role of the antigen receptor signals in the recruitment of B cells to the marginal zone

The quasimonoclonal (QM) mouse provides an intelligible model to analyze the B cell selection as the competition between two major 4-hydroxy-3- nitrophenylacetyl-specific B cell populations whose BCR are comprised of the knockin V_H17.2.25 (V_HT)-encoded H chain and the λ1 or λ2 L chain. In this study, we show the QM system is useful to examine how BCR signals guide a subset of B cells to the marginal zone (MZ). Compared with the control C57BL/6 mice, the QM mice had ∼2.7-fold increased number of B cells exhibiting the MZ B cell phenotype and a larger MZ area in the spleen. Interestingly, V_HT/λ2 B cells significantly predominated over V_HT/λ1 B cells in MZ-(V_HT/λ1:V _HT/λ2 ≈ 3:7) and transitional 2-B cell subsets, while these two populations were comparable in immature, transitional 1, and mature counterparts. Thus, the biased use of λ2 in the MZ B cells may be the result of selection in the periphery. The enlargement of MZ B cell compartment and the preferred recruitment of the V_HT/λ2 B cells were further augmented by doubling the V_HT gene, but dampened by the dysfunction of Bruton's tyrosine kinase, suggesting a positive role of BCR signaling in this selection. Comparison of Ag specificity between V _HT/λ1 and V_HT/λ2 IgM mAbs revealed a polyreactive nature of the V_HT/λ2 BCR, including the reactivity with ssDNA. Taken together, it is suggested that poly reactivity (including self-reactivity) of BCR is crucial in driving B cells to differentiate into the MZ phenotype.